Nitric oxide-cGMP signal transduction in the injury, matrix expansion and progression of anti-thy1-induced renal disease of the rat

1 Introduction 1 1.1 Pathogenesis and therapy of chronic progressive renal disease 2 1.1.1 Histological and molecular characteristics 2 1.1.2 The central role of TGF-beta in renal fibrosis 2 1.1.3 The sequence of phases leading to progressive renal fibrosis 3 1.1.4 Therapeutic approaches to chronic progressive renal disease 4 1.2 The L-arginine-NO pathway in renal disease 5 1.2.1 Two faces of the L-arginine-NO pathway 5 1.2.2 NO synthases 6 1.2.3 Effects of L-arginine supplementation on renal disease 7 1.3 NO-cGMP signaling in renal disease 7 1.3.1 Distribution of NO-cGMP signaling in the glomeruli and the tubulointerstitium 8 1.3.2 The physiology of NO-cGMP signaling 10 1.3.3 The pathophysiology of NO-cGMP signaling 11 1.3.4 Pharmacological stimulators of sGC activity 11 1.4 Aim of the study 13 2 Materials and methods 14 2.1 Materials 14 2.1.1 Chemicals, tools and instruments 14 2.1.2 Computer and software 16 2.2 Animal experiments 16 2.2.1 Animals 16 2.2.2 Production of monoclonal antibody OX-7 and mAb 1-22-3 17 2.2.3 Models of anti-thy1-induced renal disease 18 Contents-II-2.2.4 Food and drinking water intakes 18 2.2.5 Drug administration 19 2.3 Experimental design 19 2.3.1 Protocol 1: NO-cGMP signal transduction in the injury phase of acute anti-thy1 glomerulonephritis (day 1 after antibody injection) 20 2.3.2 Protocol 2: NO-cGMP signal transduction in the matrix expansion phase of acute anti-thy1 glomerulonephritis (day 7 after antibody injection) 20 2.3.3 Protocol 3: NO-cGMP signal transduction in anti-thy1-induced chronic glomerulosclerosis (progression phase) 21